The Value of Preventative Dental Care: A Discrete-Choice Experiment.

Scale and polish (SP) and oral hygiene advice (OHA) are commonly provided in primary care dental practice to help prevent periodontal disease. These services are widely consumed by service users, incurring substantial cost, without any clear evidence of clinical benefit. This article aims to elicit general population preferences and willingness to pay (WTP) for preventative dental care services and outcomes. An online discrete-choice experiment (DCE) was completed by a nationally representative sample of the UK general population. Respondents each answered 10 choice tasks that varied in terms of service attributes (SP, OHA, and provider of care), outcomes (bleeding gums and aesthetics), and cost. Choice tasks were selected using a pivoted segmented experimental design to improve task realism. An error components panel logit model was used to analyze the data. Marginal WTP (mWTP) for each attribute and level was calculated. In total, 667 respondents completed the DCE. Respondents valued more frequent SP, care provided by a dentist, and personalized OHA. Respondents were willing to pay for dental packages that generated less frequent ("never" or "hardly ever") bleeding on brushing and teeth that look and feel at least "moderately clean." Respondents were willing to pay more (+£145/y) for improvements in an aesthetic outcome from "very unclean" (-£85/y) to "very clean" (+£60/y) than they were for reduced bleeding frequency (+£100/y) from "very often" (-£54/y) to "never" (+£36/y). The general population value routinely provided SP, even in the absence of reductions in bleeding on brushing. Dental care service providers must consider service user preferences, including preferences for both health and nonhealth outcomes, as a key factor in any service redesign. Furthermore, the results provide mWTP estimates that can be used in cost-benefit analysis of these dental care services.

Comparing levels of social capital in three northern post-industrial UK cities.

OBJECTIVES: A high level of 'excess' mortality (i.e. that seemingly not explained by deprivation) has been shown for Scotland compared to England & Wales and, in particular, for its largest city, Glasgow, compared to the similarly deprived postindustrial English cities of Liverpool and Manchester. The excess has been observed across all social classes, but, for premature mortality, has been shown to be highest in comparison of those of lowest socio-economic status (SES). Many theories have been proposed to explain this phenomenon. One such suggestion relates to potential differences in social capital between the cities, given the previously evidenced links between social capital and mortality. The aim of this study was to ascertain whether any aspects of social capital differed between the cities and whether, therefore, this might be a plausible explanation for some of the excess mortality observed in Glasgow. STUDY DESIGN: Cross-sectional study. METHODS: A representative survey of Glasgow, Liverpool and Manchester was undertaken in 2011. Social capital was measured using an expanded version of the Office for National Statistics (ONS) core 'Social Capital Harmonised Question Set'. Differences between the cities in five sets of social capital topics (views about the local area, civic participation, social networks and support, social participation, and reciprocity and trust) were explored by means of a series of multivariate regression models, while controlling for differences in the characteristics (age, gender, SES, ethnicity etc.) of the samples. RESULTS: Some, but not all, aspects of social capital were lower among the Glasgow sample compared to those in Liverpool and Manchester. A number of these differences were greatest among those of higher, rather than lower, SES. Levels of social participation, trust and (some measures of) reciprocity were lower in Glasgow, particularly in comparison with Liverpool. However, assessment of any potential impact of these differences is limited by the cross-sectional nature of the data. CONCLUSIONS: The analyses suggest it is at least possible that differences in some aspects of social capital could play some part in explaining Glasgow's excess mortality, especially among particular sections of its population (e.g. those of higher SES). However, in the absence of more detailed longitudinal data, this remains speculative.

quit4u: the effectiveness of combining behavioural support, pharmacotherapy and financial incentives to support smoking cessation.

The 'quit4u' stop smoking service (SSS) was developed by National Health Service (NHS) Tayside for smokers in deprived areas of Dundee (UK). quit4u combined behavioural support and pharmacotherapy with financial incentives for each week that participants remained quit. A quasi-experimental study was undertaken with smokers using quit4u between 2009 and 2011 compared with smokers using SSSs in the rest of Scotland. The outcome measures were: number of quit attempts; quit rates at 1, 3 and 12 months; cost-effectiveness. Mechanisms of change were explored through quantitative and qualitative research that explored the views and experiences of service users and professionals involved in quit4u. The number of quit attempts made using SSSs in deprived areas of NHS Tayside increased by 44% between 2007 and 2010. quit4u had significantly higher quit rates at 1 month (49.9% versus 33.7%), 3 months (30.7% versus 14.2%) and 12 months (9.3% versus 6.5%) compared with similar smokers using other SSSs. The incremental cost per quitter was £2296. A combination of elements kept clients engaged and supported quit attempts: carbon monoxide (CO) tests, financial incentives, high-quality pharmacy support, rolling groups and greater varenicline use. quit4u may provide an effective and cost-effective model for engaging and supporting smokers in deprived areas to quit.

A randomised controlled trial of post-operative radiotherapy following breast-conserving surgery in a minimum-risk population. Quality of life at 5 years in the PRIME trial.

OBJECTIVES: To assess whether omission of post-operative radiotherapy (RT) in women with 'low-risk' axillary node-negative breast cancer [tumour size of less than 5 cm (T0-2) although the eligibility criteria further reduce the eligible size to a maximum of 3 cm] treated by breast-conserving surgery and endocrine therapy improves quality of life and is more cost-effective. DESIGN: A randomised controlled clinical trial, using a method of minimisation balanced by centre, grade of cancer, age, lymphovascular invasion and preoperative endocrine therapy was performed. SETTING: Breast cancer clinics in cancer centres in the UK. PARTICIPANTS: Patients aged ≥ 65 years were eligible provided that their breast cancers were considered to be at low risk of local recurrence, they were suitable for breast conservation surgery, they were receiving endocrine therapy and they were willing and able to give informed consent. INTERVENTIONS: The standard treatment of post-operative whole breast irradiation or the omission of RT. MAIN OUTCOME MEASURES: Quality of life was the primary outcome measure, together with anxiety and depression and cost-effectiveness. Secondary outcome measures were recurrence rates and survival, and treatment-related morbidity. The principal method of data collection was by questionnaire, completed at home with a research nurse on four occasions over 15 months, then by postal questionnaire at 3 and 5 years after surgery. RESULTS: The hypothesised improvement in overall quality of life with the omission of RT was not seen in the summary domains of the European Organisation for Research in the Treatment of Cancer (EORTC) scales. Some differences were apparent within subscales of the EORTC questionnaires, and insights into the impact of treatment were also provided by the qualitative data obtained by open-ended questions added by the trial team. Differences were most apparent shortly after the time of completion of RT. RT was then associated with increased breast symptoms and with greater (self-reported) fatigue, but with lower levels of insomnia and endocrine side effects. These statistically significant differences in breast symptoms persisted for up to 5 years after RT [mean difference, RT was 5.27 units greater than no RT, 95% confidence interval (CI) of 1.46 to 9.07], with similar, though non-significant, trends in insomnia. No significant difference was found in the overall quality of life measure, with the no RT group having 0.36 units greater quality of life than the RT group (95% CI -5.09 to 5.81). CONCLUSIONS: Breast RT is tolerated well by most older breast cancer patients without impairing their overall health-related quality of life (HRQoL). Although HRQoL should always be taken into account when determining treatment, our results show that the addition of RT does not impair overall quality of life. Further economic modelling on the longer-term costs and consequences of omitting RT is required. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14817328. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 15, No. 12. See the HTA programme website for further project information.

Community photo-triage for skin cancer referrals: an aid to service delivery.

BACKGROUND: We wished to investigate the potential for extending the capacity of the specialist service by using community-based photo-triage for suspected skin cancers. AIMS: To compare the outcomes and costs of conventional and photo-triage referral pathways. METHODS: This was an observational study of conventional and photo-triage referrals. Patients referred for initial photo-triage were invited to visit a medical photographer located in community health centres, who would take high-quality close-up and dermatoscopic images of the patients' lesions. A dermatologist then reviewed the images, and triaged patients to specific treatment clinics. All patients referred by conventional letter were offered initial appointments at the consultant-delivered skin cancer clinic. The difference in costs was assessed by modelling health service use under both pathways. RESULTS: Photo-triage permitted 91% of patients (263/289) to achieve definitive care at first visit to the specialist team, compared with only 63% (117/186) via the conventional referral pathway. The mean waiting time to definitive treatment for patients with skin cancer was slightly reduced with photo-triage. Photo-triage permitted direct booking for 45% of patients to attend a nurse-delivered clinic, 22% to attend directly for surgery, 2% to attend a community general practice clinic and 2% to be referred on electronically to another specialty. This reduced by 72% the number of patients requiring attendance to the consultant clinic, freeing up capacity. Despite the cost of providing medical photography, there was a small cost saving of around £ 1.70 per patient using photo-triage. CONCLUSIONS: Community photo-triage improved referral management of patients with suspected skin cancer, improving the delivery of definitive care at first visit and achieved an increased service capacity. Cost comparison found that the photo-triage model described was marginally cheaper than conventional care, and reduced hospital visits. An integrated primary-secondary care referral pathway that includes photo-triage facilitates a more efficient specialist service while ensuring that all suspicious lesions are viewed by an experienced dermatologist.

A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population. The PRIME trial.

OBJECTIVES: To assess whether omission of postoperative radiotherapy in women with 'low-risk' axillary node negative breast cancer (T0-2) treated by breast-conserving surgery and endocrine therapy improves quality of life and is more cost-effective. DESIGN: A randomised controlled clinical trial, using a method of minimisation balanced by centre, grade of cancer, age, lymphatic/vascular invasion and preoperative endocrine therapy, was performed. A non-randomised cohort was also recruited, in order to complete a comprehensive cohort study. SETTING: The setting was breast cancer clinics in cancer centres in the UK. PARTICIPANTS: Patients aged 65 years or more were eligible provided that their cancers were considered to be at low risk of local recurrence, were suitable for breast-conservation surgery, were receiving endocrine therapy and were able and willing to give informed consent. INTERVENTIONS: The standard treatment of postoperative breast irradiation or the omission of radiotherapy. MAIN OUTCOME MEASURES: Quality of life was the primary outcome measure, together with anxiety and depression and cost-effectiveness. Secondary outcome measures were recurrence rates, functional status, treatment-related morbidity and cosmesis. The principal method of data collection was by questionnaire, completed at home with a research nurse at four times over 15 months. RESULTS: The hypothesised improvement in overall quality of life with the omission of radiotherapy was not seen in the EuroQol assessment or in the functionality and symptoms summary domains of the European Organisation for Research in the Treatment of Cancer (EORTC) scales. Some differences were apparent within subscales of the EORTC questionnaires, and insights into the impact of treatment were also provided by the qualitative data obtained by open-ended questions. Differences were most apparent shortly after the time of completion of radiotherapy. Radiotherapy was then associated with increased breast symptoms and with greater fatigue but with less insomnia and endocrine side-effects. Patients had significant concerns about the delivery of radiotherapy services, such as transport, accommodation and travel costs associated with receiving radiotherapy. By the end of follow-up, patients receiving radiotherapy were expressing less anxiety about recurrence than those who had not received radiotherapy. Functionality was not greatly affected by treatment. Within the randomised controlled trial, the Barthel Index demonstrated a small but significant fall in functionality with radiotherapy compared with the no radiotherapy arm of the trial. Results from the non-randomised patients did not confirm this effect, however. Cosmetic results were better in those not receiving radiotherapy but this did not appear to be an important issue to the patients. The use of home-based assessments by a research nurse proved to be an effective way of obtaining high-quality data. Costs to the NHS associated with postoperative radiotherapy were calculated to be of the order of 2000 pounds per patient. In the follow-up in this study, there were no recurrences, and the quality of life utilities from EuroQol were almost identical. CONCLUSIONS: Although there are no differences in overall quality of life scores between the patients treated with and without radiotherapy, there are several dimensions that exhibit significant advantage to the omission of irradiation. Over the first 15 months, radiotherapy for this population is not a cost-effective treatment. However, the early postoperative outcome does not give a complete answer and the eventual cost-effectiveness will only become clear after long-term follow-up. Extrapolations from these data suggest that radiotherapy may not be a cost-effective treatment unless it results in a recurrence rate that is at least 5% lower in absolute terms than those treated without radiotherapy. Further research is needed into a number of areas including the long-term aspects of quality of life, clinical outcomes, costs and consequences of omitting radiotherapy.

Successes and challenges in a field-based, multi-method study of home telehealth.

We are conducting a three-year study of telehealth in 11 home care offices that serve rural clients in Alberta. Three hundred and twenty palliative home care clients are being recruited to participate in a randomized controlled trial (RCT) to answer three questions about the use of video-phones and their effect on symptom management, quality of life and cost, as well as readiness to use the technology. Both successes and challenges have been identified in three main areas: technology, people/organizational issues and study design. Maintaining study integrity has been the key factor in decision making, as adjustments from the original proposal are made. It is already clear that field-based RCTs are feasible, but require commitment and flexibility on the part of researchers and community partners to work through the study implementation.

MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia.

Outgrowth of minimal residual disease (MRD) in acute myeloid leukaemia (AML) is responsible for the occurrence of relapses. MRD can be quantified by immunophenotyping on a flow cytometer using the expression of leukaemia-associated phenotypes. MRD was monitored in follow-up samples taken from bone marrow (BM) of 72 patients after three different cycles of chemotherapy and from autologous peripheral blood stem cell (PBSC) products. The MRD% in BM after the first cycle (n=51), second cycle (n=52) and third cycle (n=30), as well as in PBSC products (n=39) strongly correlated with relapse-free survival. At a cutoff level of 1% after the first cycle and median cutoff levels of 0.14% after the second, 0.11% after the third cycle and 0.13% for PBSC products, the relative risk of relapse was a factor 6.1, 3.4, 7.2 and 5.7, respectively, higher for patients in the high MRD group. Also, absolute MRD cell number/ml was highly predictive of the clinical outcome. After the treatment has ended, an increase of MRD% predicted forthcoming relapses, with MRD assessment intervals of < or =3 months. In conclusion, MRD parameter assessment at different stages of disease is highly reliable in predicting survival and forthcoming relapses in AML.

A flow cytometric method to detect apoptosis-related protein expression in minimal residual disease in acute myeloid leukemia.

Minimal residual disease (MRD) cells are thought to be responsible for the persistence and relapse of acute myeloid leukemia (AML). Flow cytometric MRD detection by the establishment of a leukemia-associated phenotype (LAP) at diagnosis can be used in 80% of AML patients, allowing detection and functional characterization of MRD in follow-up bone marrow. One of the mechanisms contributing to inefficient chemotherapy is apoptosis resistance. Measuring apoptosis parameters in MRD cells will help to unravel the importance of apoptosis resistance in AML. We therefore developed a four-color flow cytometry method that enables establishment of apoptosis-related protein expression such as Bcl-2, Bcl-x(L), Mcl-1 and Bax at diagnosis and in MRD. Firstly, validation of this assay using Western blot analysis in five leukemia cell lines showed a significant correlation (R=0.70: P<0.0001). Secondly, the influence of the permeabilization procedure on LAP expression was investigated in 38 AML samples at diagnosis and in 42 MRD samples. Quantification of the frequency of LAP+ cells with and without permeabilization showed no significant differences (diagnosis: P= 0.57, follow-up: P= 0.43). The flow cytometric protocol thus enables analysis of apoptosis-related proteins at different stages of the disease, which will lead to a better understanding of the role of apoptosis resistance in the emergence of MRD in AML.

High percentage of CD34-positive cells in autologous AML peripheral blood stem cell products reflects inadequate in vivo purging and low chemotherapeutic toxicity in a subgroup of patients with poor clinical outcome.

In this study, a high CD34% in autologous peripheral blood stem cell (PBSC) products from 71 AML patients was associated directly with a high relapse rate (P = 0.006) and inversely with disease-free survival (P = 0.003), irrespective whether patients were transplanted or not. The relapse rate at 12 months was 67% in a group with >0.8% CD34+ cells and 34% in a group with < or = 0.8% CD34+ cells. Although the percentage of malignant CD34+ cells in the CD34+ compartment in the relapses of the first group was not high (median 8%), the total number of malignant cells as a percentage of WBC was about 13 times higher than for the patients remaining >12 months in remission. When all patients evaluable were taken together, this frequency of malignant cells correlated strongly with disease-free survival (P < 0.001). Both this massive mobilization of normal CD34+ cells and high frequency of malignant cells in the subgroup of patients with CD34 >0.8% and relapse within 12 months indicate an insufficient in vivo purging, as well as low chemotherapeutic bone marrow toxicity. This was confirmed by an inverse correlation between hypoplasia period after the induction therapy and CD34% in PBSC products (P < 0.002). It is concluded that a subgroup of patients has been identified that might benefit from a more intensive chemotherapeutic treatment.

Access to specialist cancer care: is it equitable?

The first principle of the Calman-Hine report's recommendations on cancer services was that all patients should have access to a uniformly high quality of care wherever they may live. This study aimed to assess whether the uptake of chemotherapy for colorectal cancer varied by hospital type in Scotland. Hospitals were classified according to cancer specialisation rather than volume of patients. To indicate cancer specialisation, hospitals were classified as 'cancer centres', 'cancer units' and 'non-cancer' hospitals. Colorectal cancer cases were obtained from cancer registrations linked to hospital discharge data for the period January 1992 to December 1996. Multilevel logistic regression was used to model the binary outcome, namely whether or not a patient received chemotherapy within 6 months of first admission to any hospital. The results showed that patients admitted first to a 'non-cancer' hospital were less than half as likely to go on to receive chemotherapy as those first admitted to a cancer unit or centre (OR=0.28). This result was not explained by distance between hospital of first admission and nearest cancer centre, nor by increasing age or severity of illness. The study covers the period immediately preceding the introduction of the Calman-Hine report in Scotland and should serve as a baseline for future monitoring of access to specialist care.

Activity and expression of the multidrug resistance proteins P-glycoprotein, MRP1, MRP2, MRP3 and MRP5 in de novo and relapsed acute myeloid leukemia.

The multidrug resistance proteins (MRPs) MRP1, MRP2, MRP3, MRP5 and P-glycoprotein (P-gp) act in concert with each other to give a net resultant pump function in acute myeloid leukemia (AML). The aim of the present study was to analyze the activity of these proteins, which might be upregulated at relapse as compared with de novo AML due to clonal selection. The mRNA expression and activity of P-gp and the MRPs were determined with RT-PCR and flow cytometry, in conjunction with phenotype, as measured with the monoclonal antibodies CD34, CD38 and CD33, in 30 paired samples of de novo and relapsed AML. P-gp and MRP activity varied strongly between the cases (rhodamine 123 efflux-blocking by PSC833: 5.4+/-7.7, and carboxyfluorescein efflux-blocking by MK-571: 4.3+/-6.7, n = 60). P-gp and MRP activity were increased in 23% and 40% of the relapse samples, and decreased in 30% and 20% of the relapse samples, respectively (as defined by a difference of >2 x standard deviation of the assays). Up- or downregulation of mRNA expression was observed for MDR1 (40%), MRP1 (20%), MRP2 (15%), MRP3 (30%), and MRP5 (5%). Phenotyping demonstrated a more mature phenotype in 23% of the relapsed AML cases, and a more immature phenotype in 23% of the relapses, which was independent of the karyotypic changes that were observed in 50% of the studied cases. P-gp and MRP activity correlated with the phenotypic changes, with higher P-gp and MRP activities in less mature cells (r = -0.66, P < 0.001 and r = -0.31, P = 0.02, n = 58). In conclusion, this study shows that P-gp and MRP activity are not consistently upregulated in relapsed AML. However, P-gp and MRP activities were correlated with the maturation stage as defined by immune phenotype, which was observed to be different in 46% of the relapses.

Functional characterization of minimal residual disease for P-glycoprotein and multidrug resistance protein activity in acute myeloid leukemia.

Relapse is common in acute myeloid leukemia (AML) due to persistence of residual leukemia cells: minimal residual disease (MRD). In 102 out of 127 patients (80%), cells at diagnosis displayed one or more leukemia-associated phenotypes (LAP), ie combinations of cell surface markers which are absent in normal cells and can thus be used to detect MRD at follow-up. Functional characterization of MRD cells for P-glycoprotein (Pgp) and multidrug resistance protein (MRP) activity is essential to investigate the role of these drug transport proteins in multidrug resistance in AML. A fluorescent probe assay using Syto16/PSC833 and calcein-AM/probenecid as substrate/modulator of the Pgp and MRP pump, respectively, and subsequent labeling of cells with monoclonal antibodies for LAP detection allowed simultaneous detection of LAP and Pgp or MRP activity. Validation of this assay is shown for 30 newly diagnosed AML and 11 MRD situations. In addition, no significant differences were found when comparing fresh and cryopreserved de novo AML for LAP expression (n = 43), Pgp (n = 30) and MRP (n = 24) function and for MRD samples for simultaneous LAP expression and Pgp/MRP activity (n = 10). This approach enables longitudinal and multicenter studies on the detection, quantification and functional characterisation of MRD cells.

Assessing the resource implications of extending routine invitation to breast screening to women aged 65-67 years.

UK breast screening policy currently restricts routine 3-yearly invitation to screening to 50-64 year olds. However, it is likely that routine invitation will be extended to 65-67 year olds in 2001. This paper first predicts the additional demand for breast screening as a result of this new policy by modelling the response to the 1998 invitation of women eligible for screening in 2001. The independent variables include (i) the woman's characteristics: her screening history; the deprivation score of the area she lives in; and (ii) the characteristics of the screening: whether the screening took place in a mobile van or at a static site; and time of the year. The modelling of attendance is quite successful in that most hypothesised variables have the expected sign. It is estimated that an additional 10829 women will be screened per annum. The additional invitation, screening and assessment costs are expected to be approximately pound350000 in 2001.

Estimating time preferences for health using discrete choice experiments.

This study is the first to use discrete choice experiments to elicit inter-temporal preferences for health. Inter-temporal preferences with respect to one's own future health are compared with inter-temporal preferences with respect to others' future health. Discrete choice experiments are used to measure the relative importance of the duration of ill-health and how far in the future the ill-health occurs. Data were collected by postal questionnaire in the UK. The median implied rates of discount range from 0.055 to 0.091 for own health, depending on the period of delay, and from 0.078 to 0.147 for others' health. The implied discount rate varies with respect to age, self-rated health, and version of the questionnaire. The implied discount rates are broadly comparable with other published estimates using closed-ended methods. One concern is the large percentage of respondents with dominant preferences. This issue needs to be explored before adopting the approach of discrete choice experiments to elicit inter-temporal preferences.

The efficient organization of blood donation: what determines the number of donors and donations?

This study investigates the influence of socio-economic characteristics on the number of donors in geographical areas in the North of Scotland as well as the influence of panel-specific characteristics on the number of donations obtained from each panel in the North of Scotland. Econometric models are applied to establish the relationship between these variables. The main findings were that there was no scope for identifying new areas in which to locate new panels or extend the activities of existing panels because the number of donors in an area was closely correlated with population. There was therefore little scope for recruitment of donors by focusing on any particular area. It was found that annual donations per panel are significantly influenced by the number of donors invited, the number of opportunities to donate and the average length of sessions. Combined with cost information, increasing the length of the session appears to be the most cost-effective means of collecting higher volumes.